Searching for Lost Memories Under Thousands of Microscopes

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On a cool September evening, Judy Johanson curled up on her living room sofa with her iPad, carefully examining mouse brains. Her husband, Steve, slept just a few feet away. It was granular work, especially for a woman who for 24 years ran a daycare center. Judy scrolled through hundreds of slides, searching them, one by one, for tiny black spots. The task might have appeared deeply tedious—but Judy was in the zone. While Steve dreamed, she was joining thousands of amateur scientists in the search for a cure for his disease.

When Steve was diagnosed with younger-onset Alzheimer’s disease six years ago, at age 58, he told Judy: “We can choose to be sad or we can choose to be happy.” So they chased happiness: The Johansons worked with the Alzheimer's Association and began lobbying local and federal politicians for more research funding. Until last November, Steve was part of a promising 18-month clinical trial for a drug intended to slow his cognitive decline. Judy felt certain that the drug was working, but earlier this year researchers concluded it was ineffective.

The news was crushing. Since then, Steve’s experienced a significant decline. His mobility is limited; Judy converted their living room into a bedroom so that he doesn’t have to use the stairs. One day this summer, he walked straight into the swimming pool that he’d constructed in their backyard nine years earlier. As Steve’s symptoms have worsened, it’s become harder to find trials for which he qualifies; at times, a treatment can feel impossibly far away. He no longer remembers telling Judy they should “choose to be happy.”

But Judy has found solace in sorting through the slides of tiny mouse brains that might hold the key to Steve’s recovery. She’s one of six thousand people who have logged time playing Stall Catchers, a game that helps researchers investigate how treating the impaired cerebral blood flow associated with Alzheimer’s can help reverse memory loss. (In mice, lab researchers have found, it can.) By turning the research into an online game, its creators hope to speed up lab research—and hopefully lead to a treatment for the disease in a few years, as opposed to a few decades.

Stall Catchers is a little different. Yes, plenty of its players are the same quirky enthusiasts and retirees that go gaga for crowdsourced astronomy and history projects (and sometimes even wind up with their names on scientific papers). But at the game’s heart is a community of people like Judy Johanson, who have watched a loved one struggle with Alzheimer’s and are desperate for some way to feel like they are doing something concrete to fight the disease. Frustrated by high nonprofit overheads and the glacial pace of research, they’ve leapt at an opportunity to take things into their own hands. And though a true cure for Alzheimer’s is still distant, Stall Catchers has already proven an effective treatment for one of the disease’s most insidious symptoms: helplessness.

At the rate that Nozomi Nishimura and Chris Schaffer’s research was going, it was going to take decades to bring a treatment to market. The Cornell biomedical engineering professors had spent eight years investigating the relationship between impaired blood flow in the brain and Alzheimer’s disease. They’d figured out how to examine the smallest blood vessels in the brains of mice that were genetically modified to mimic Alzheimer's. They’d discovered that they were able to reverse some memory loss with a drug to improve blood flow. But that drug also destroyed the mice’s ability to fight infections, making it unfit for humans. Now, the lab is trying to find a drug that can tackle “stalls”—places where blood flow has been cut off—without compromising patients’ immune systems. That means that for every drug they test, they need to examine images of the mice’s brains and search for stalls, which show up on the slides as small black spots and indicate that the drug isn’t working. But testing a new drug requires that some 30,000 images be examined—a process that would take the lab as long as a year for each new experiment.

Enter Pietro Michelucci. The director of the Human Computation Institute had spent years studying collective intelligence systems, which harness the wisdom of crowds in decision-making, and he’d created the nonprofit to apply that crowd power to real-world problems. A colleague put Michelucci in touch with Schaffer. The Cornell lab’s mountain of visual data reminded Michelucci of Stardust@Home, a pioneering citizen science project that deputized amateurs to analyze interstellar dust collected during NASA’s 1999 Stardust sample mission. Michelucci was sure he could apply the virtual microscope used to catalogue space dust to the Schaffer-Nishimura lab’s images. (The creator of Stardust@Home, Andrew Westphal, had lost his father to Alzheimer’s and didn't take much convincing.)

But Nishimura and Schaffer were skeptical. They’d spent a long time individually training undergraduates to analyze the images properly. How could thousands of amateurs with little to no background in science possibly be trusted to get it right?

A slide of a mouse brain, in need of Stall Catchers’ analysis.

STALL CATCHERS

The key, it turned out, was an algorithm that Michelucci developed to tap the wisdom of the crowd. It counts every “stall” identified by a volunteer as a vote—either in favor of or against that image representing a genuine disruption in blood flow. A critical mass of votes produces a verdict with similar accuracy to one from a trained scientist. Michelucci calls this the “magic number,” and he’s managed to bring it down from 20 to 7 through a weighted system that gives more credence to votes from volunteers who’ve been playing for longer.

The crowdsourcing is already leading to results in the lab. Earlier this month, Michelucci announced that the Stall Catchers crowd had helped determine that stalls in blood flow are not associated with the amyloid plaques that are a hallmark of Alzheimer’s disease—a finding that will help the Cornell researchers narrow down their exploration of treatment options. Michelucci and his team have held “catch-a-thons” across the world, and recruited players from over 14 countries. At peak moments of productivity, Stall Catchers players have completed a week’s worth of lab research in a single hour.

It’s still slow work; “disappointingly slow,” Nishimura says. A cure won’t emerge tomorrow. With the help of Stall Catchers, the lab might be able to offer a treatment in a fraction of the time it would otherwise—but still, we’re talking years. For people like Judy and Steve Johanson, however, that could make a difference.

The Johansons never saw their lives going in this direction when they met 42 years ago, at a Boys & Girls club. Judy was 12, Steve was 22, and Judy harbored a crush on him for six years before they began dating. Seven years later, they moved into the house in Watertown, Massachusetts where they still live today, sharing a backyard with Judy’s mother and sister. They raised a daughter and a son. Steve’s brother married one of Judy’s sisters. Steve worked as a construction project manager, and he constantly made additions to their property: He built the inground pool, and added on a townhouse, where their daughter and her husband now live. While Judy ran a daycare, Steve managed $20 million projects at Northeastern University, across the Charles River.

Six years ago, Steve got an unusually negative performance review at work— and five months later, he received his devastating diagnosis. At one point, he told Judy that he wished he had a brain tumor, because then at least there might be treatment options. In a journal entry composed shortly after his diagnosis, Steve reflected: “As a construction manager and a carpenter, I have always been able to put the pieces together to build beautiful and safe places for my family, friends, co-workers. I suspect my tools will lay, unused and layered with ever-deepening layers of dust.”

These days, Steve and Judy wake as early as three or five in the morning, and Judy helps him shower, dress, and brush his teeth. Three days a week Judy drives him to a daycare program, where he plays trivia games, listens to music, or catches up on the news. Lately, Steve has found the news distressing: He worries that Donald Trump is going to come and harm his children; he’s become convinced that the hurricanes ravaging Texas, Florida, and the Caribbean are going to reach Massachusetts. He wants to know when the family is going to evacuate. That has effectively quashed Judy’s desire to catch up on current events. So in her rare moments of free time, she turns to those black-and-white, grainy stills of mouse brains.

Stall Catchers is hardly Candy Crush. The images can be difficult to parse, and analyzing them can sometimes feel more like homework for a high-school science class than an entertaining game. Still, it’s become something of a family tradition in the Johanson household. Judy’s sister, Kelly Corrigan, plays incessantly—while on the stairmaster at the gym; in the waiting room at the dentist’s office or the DMV; or in lieu of watching TV in the evening. The Johanson’s two oldest grandchildren—Nathan, who’s 7 years old, and Caleb, who’s 9—have become adept at catching stalls, too, and sometimes even outscore Judy, who says she’s more prone to becoming trigger-shy when she’s missed a stall or two. Together, Kelly and Judy have recruited nearly 100 people to join them on the leaderboard.

They describe themselves as addicted to the game, and though it may be difficult to believe that picking through mouse brains could be addictive, they’re not alone. By adding in the simple element of a scoreboard, the game’s creators have tapped into players’ competitive instincts—and the more you play, the more points you get for every correctly spotted stall. The game is a hit among kids—at Lake Hazel Middle School in Boise, Idaho, for instance, a teacher named Erin Davies recruited 240 students to play, and many of them have cracked the top 50 on the leaderboard. None have come close, however, to unseating Michael Capraro, a retired chemical engineer living in Riverview, Michigan who plays Stall Catchers for a solid hour and a half every day in order to maintain his #1 spot on the leaderboard, where he boasts a score of 285,778,531 (for context, your first few stall catches will earn you just 10 points each).

Judy and Kelly are full of tips and tricks for mastering Stall Catchers—number one, play it on a computer or an iPad, not on your phone—and the family will often gather in a room with Steve and spend an afternoon or evening catching stalls. “It’s something we can all do together, when there’s a lot of things we can’t do together anymore,” says Judy. “There’s nothing, really nothing you can do for this disease. This is hope in a video game.”

In an ideal world, no one would need to spend unpaid hours examining mouse brains. Stall Catchers is a workaround. Alzheimer’s research has long been underfunded: In 2016, the federal government spent $986 million on research, when the Alzheimer’s Association has long maintained that researchers need $2 billion per year in order to treat the disease effectively. There was some positive progress on that front earlier this month, when the Senate Labor, Health and Human Services, and Education Appropriations Subcommittee approved $414 million in new spending for research on Alzheimer’s disease, bringing the total that the NIH will spend on the disease this year up to $1.8 billion. That was heartening for Judy: When she and Steve first started advocating for more funding four years ago, the budget was at just $504 million.

The Johansons are realistic. They know that no amount of stall catching will necessarily help Steve. For their close friend Sheryl Teti, it’s already too late: Her father died nearly two years ago, at the age of 85, after spending five years wrestling with Alzheimer’s. Stall Catchers didn’t exist when Teti’s father was struggling—but she now finds herself playing it nearly every day, sometimes for as many as three hours. “You don’t have to wait for the walk or the triathlon to do this,” she says. “You can do this whenever you need to.”

It can be difficult, Judy says, to be hopeful for a cure yet accepting of the fact that one might not come soon enough. When the hopefulness feels particularly out of reach, she borrows a phrase coined by her grandkids: “When life gives you Alzheimer’s, make lemonade.” Her grandchildren literally make lemonade, donating the proceeds to the Alzheimer’s Association. And Judy? She catches stall, after stall, after stall.